今日の臨床サポート

黄体機能不全

著者: 杉野法広 山口大学 産科婦人科学

監修: 杉野法広 山口大学 産科婦人科学

著者校正/監修レビュー済:2020/09/03
参考ガイドライン:
  1. 日本産科婦人科学会:産婦人科診療ガイドライン 婦人科外来編2020
  1. 日本生殖医学会:生殖医療の必修知識2017
患者向け説明資料

概要・推奨   

  1. 黄体機能不全は単一の病因による疾患ではなく、多くの病態や病因が含まれている(推奨度2)
  1. 黄体期中期の検査として子宮内膜の厚さの評価も重要である(推奨度1)
  1. 子宮内膜日付診の異常がある場合は、これに対しての特別な治療はない。HCG による黄体賦活療法か、または黄体ホルモンの補充療法が選択される(推奨度2)
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
杉野法広 : 研究費・助成金など(浜田市,あすか製薬)[2021年]
監修:杉野法広 : 研究費・助成金など(浜田市,あすか製薬)[2021年]

改訂のポイント
  1. 近年では、基礎体温、血中プロゲステロン値、子宮内膜日付診の異常を検出することの臨床的意義は認められないため、不妊患者のスクリーニング検査としての有用性が疑問視されていることを明記した。
  1. 自然周期における黄体機能不全の治療法として、黄体ホルモン補充療法やHCG による黄体賦活療法の有効性は示されていないことを明記した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 黄体機能不全(luteal phase defect)とは、黄体からのプロゲステロンの分泌不全により、子宮内膜の分泌性変化が完全に起こらないものと定義されている。しかし、実際には黄体からのホルモン分泌に異常がなくても子宮内膜の変化に異常がある場合もあり、子宮内膜自体の異常も含めて黄体機能不全を取り扱っているのが現状である。
  1. 黄体機能不全とは、黄体からのプロゲステロンの分泌不全によって引き起こされる着床障害、または分泌期子宮内膜自体の異常によって引き起こされる着床障害と考えられる。
  1. 黄体機能不全は単一の病因による疾患ではなく、多くの病態や病因が含まれていることに注意する。
  1. 黄体機能不全は不妊症、反復流産、習慣性流産の原因として重要である。
  1. 頻度は、不妊患者においては10~50%、反復流産患者においては25~60%。
  1. 黄体機能不全が認められた場合、次の周期も連続して黄体機能不全になる頻度は、50~80%と高頻度である。
問診・診察のポイント  
  1. 月経周期を確認する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

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文献 

著者: A Nyboe Andersen, B Popovic-Todorovic, K T Schmidt, A Loft, A Lindhard, A Højgaard, S Ziebe, F Hald, B Hauge, B Toft
雑誌名: Hum Reprod. 2002 Feb;17(2):357-61.
Abstract/Text BACKGROUND: The aim was to study whether prolongation of luteal support during early pregnancy influences the delivery rate after IVF.
METHODS: Dual centre study including 303 women who achieved pregnancy after IVF or ICSI was used. All were treated with the long protocol using GnRH agonists and given luteal support with 200 mg vaginal progesterone three times daily during 14 days from the day of transfer until the day of a positive HCG test. The study group (n = 150) withdrew vaginal progesterone from the day of positive HCG. The control group (n = 153) continued administration of vaginal progesterone during the next 3 weeks of pregnancy.
RESULTS: The number of miscarriages prior to and after week 7 of gestation was seven (4.6%) and 15 (10.0%) in the study group and five (3.3%) and 13 (8.5%) in the control group respectively. The number of deliveries was 118 (78.7 %) in the study group and 126 (82.4 %) in the control group. The differences were not significant.
CONCLUSIONS: Prolongation of progesterone supplementation in early pregnancy has no influence on the miscarriage rate, and thus no effect on the delivery rate. Progesterone supplementation can safely be withdrawn at the time of a positive HCG test.

PMID 11821278  Hum Reprod. 2002 Feb;17(2):357-61.
著者: T Ayabe, O Tsutsumi, M Momoeda, T Yano, N Mitsuhashi, Y Taketani
雑誌名: Fertil Steril. 1994 Apr;61(4):652-6.
Abstract/Text OBJECTIVE: To determine whether luteal phase defect (LPD) is associated with follicular growth or LH surge.
DESIGN: The length of luteal phase was determined by the date of ovulation assessed by serial ultrasound measurements of follicle growth on a daily basis. Luteal phase defect was defined when the length of the luteal phase was < 11 days and/or the midluteal serum P level was < 10 ng/mL (31.8 nmol/L). Preovulatory follicular growth was examined by transvaginal ultrasonography. Blood samples taken at midluteal phase were assayed for P. Urine LH levels were determined in samples collected twice a day during periovulatory cycles using rapid urinary assay kits.
SETTING: Infertility outpatient clinic, Tokyo University Hospital.
PATIENTS: Eighty-one menstrual cycles from 63 normally cycling infertile women who were not administered any medications.
RESULTS: Thirty-six of 81 cycles showed LPD. The mean +/- SD maximal preovulatory follicular diameter was significantly smaller in LPD cycles than in non-LPD cycles (16.5 +/- 2.7 versus 19.0 +/- 2.8 mm). The mean +/- SD peak level of urinary LH surge was significantly lower in LPD cycles compared with non-LPD cycles (50 +/- 25 versus 65 +/- 21 IU/L). Luteal phase defect cycles showed a relatively high incidence of abnormal LH surges, namely, lower peak levels or prolonged duration.
CONCLUSIONS: Luteal phase defect was associated with impaired follicular growth and/or abnormal LH surge. These factors may be involved in the pathogenesis of LPD.

PMID 8150106  Fertil Steril. 1994 Apr;61(4):652-6.
著者: B Hinney, C Henze, W Kuhn, W Wuttke
雑誌名: J Clin Endocrinol Metab. 1996 Feb;81(2):565-70. doi: 10.1210/jcem.81.2.8636268.
Abstract/Text The pulsatile release pattern of LH during the entire menstrual cycle is well defined; however, the response of corpora lutea to these LH pulses in patients suffering from corpus luteum insufficiencies (CLI) is largely unknown. Patients suffering from CLI were selected from infertile patients on the basis of low progesterone (P < 25 nmol/L) in a blood sample withdrawn during a monitoring cycle. During the next cycle, nine blood samples were collected during the follicular and luteal phase and follicular development was assessed by vaginal sonography. Of 109 patients who had a CLI in the monitoring cycle, 55 had a CLI again, and 38 women agreed to undergo assessment of pulsatile hormone secretion. These women again had P < 25 nmol/L at days 6 and 7 of the luteal phase and blood samples were withdrawn through antecubital vein catheters from 0900-1700 h at 10-min intervals on days 7, 8, or 9 following ovulation. From 38 patients with such defined CLI, 16 (42%) had no LH episode and significantly lower basal LH levels in comparison with 14 control subjects. Thirteen (34%) of the patients had normal appearing LH episodes despite too low P and E2 concentrations, but their CL did not react to the LH episodes. The remaining 9 patients (24%) had normal LH episodes; their CL reacted to these episodes, but their basal P levels were too low. In all blood samples LH was not only determined using an immunoassay but also by the mouse Leydig cell testosterone production bioassay. It could be established that no CLI exists, which is due to the release of bioinactive LH. It is anticipated that the differentiation of three different types of CLI, one of hypothalamic and two of ovarian origin, may allow the development of differential diagnostic and therapeutic tools in the future.

PMID 8636268  J Clin Endocrinol Metab. 1996 Feb;81(2):565-70. doi: 10・・・
著者: A Tavaniotou, C Albano, J Smitz, P Devroey
雑誌名: Hum Reprod. 2001 Apr;16(4):663-7.
Abstract/Text Luteinizing hormone (LH) is mandatory for the maintenance of the corpus luteum. Ovarian stimulation for IVF has been associated with a defective luteal phase. The luteal phases of two groups of patients with normal menstrual cycles and no endocrinological cause of infertility were retrospectively analysed in IVF cycles. Thirty-one infertile patients stimulated with human menopausal gonadotrophins (HMG) for IVF to whom the gonadotrophin-releasing hormone (GnRH) antagonist Cetrorelix 0.25 mg was also administered to prevent the LH surge (group I) were compared with 31 infertile patients stimulated with HMG alone (group II). Despite differences in the stimulation outcome, luteal LH serum concentrations were similar in the two groups. LH values dropped from 2.3 +/- 1 IU/l on the day of human chorionic gonadotrophin (HCG) administration to 1.1 +/- 0.7 IU/l on day HCG +2 in group I (P < 0.0001) and from 5.1 +/- 3 to 1.2 +/- 1.7 IU/l (P < 0.0001) in group II. In the mid-luteal phase, LH concentrations were low in both groups. Our results suggest that suppressed LH concentrations in the early and mid-luteal phase may not be attributed solely to the GnRH-antagonist administration. Pituitary LH secretion may be inhibited by supraphysiological steroid serum concentrations via long-loop feedback and/or by the central action of the exogenously administered HCG via a short-loop mechanism.

PMID 11278214  Hum Reprod. 2001 Apr;16(4):663-7.
著者: N Sugino, S Takiguchi, M Ono, H Tamura, K Shimamura, Y Nakamura, R Tsuruta, D Sadamitsu, T Ueda, T Maekawa, H Kato
雑誌名: Hum Reprod. 1996 Nov;11(11):2484-7.
Abstract/Text To study the relationship between follicular atresia, apoptosis, and nitric oxide (NO) generation in follicular development, steroidogenesis, NO levels in follicular fluid and apoptosis were analysed in the various sized follicles of women receiving ovarian stimulation with human menopausal gonadotrophin (HMG)-human chorionic gonadotrophin (HCG) treatments for in-vitro fertilization (IVF)-embryo transfer. The follicles were divided into three groups by diameter: large follicle, > or = 18 mm; medium follicle, > or = 12 and < or = 15 mm; small follicle, < or = 10 mm. Follicular fluid was obtained from 20 women 34 h after HCG administration, and the concentrations of oestradiol, progesterone and testosterone, and nitrite, nitrate, arginine and citrulline were measured. Granulosa cells obtained from each group of follicular fluid were stained with Hoechst dye, and nuclear morphology was examined by a fluorescence microscopy. Oestradiol and progesterone concentrations in large follicles were significantly (P < 0.01) higher than those in medium or small follicles, and testosterone concentrations in small follicles were significantly (P < 0.01) higher than those in large follicles. There were no significant differences in the concentrations of nitrite, nitrate, arginine and citrulline among three groups. The percentage of apoptotic cells with nuclear fragmentation was significantly (P < 0.01) higher in small follicles than in large follicles. The present results suggested that small follicles with poor response to HMG may undergo atresia through apoptosis. No significant difference in the follicular NO level between large and small follicles led us to speculate on a different responsiveness to NO in these two types of follicles.

PMID 8981140  Hum Reprod. 1996 Nov;11(11):2484-7.
著者: T Minegishi, M Tano, Y Abe, K Nakamura, Y Ibuki, K Miyamoto
雑誌名: Mol Hum Reprod. 1997 Feb;3(2):101-7.
Abstract/Text The gonadotrophins follicle stimulating hormone (FSH) and luteinizing hormone (LH) are key hormones in the regulation of ovarian function. In the present study, the expression of LH/human chorionic gonadotrophin (HCG) receptor mRNAs in the human ovary was examined. Northern blot analysis was used to measure relative amounts of LH/HCG receptor mRNA, and in-situ hybridization was used to localize LH/HCG receptor transcripts. Northern blot analysis of human ovaries detected three transcripts (5.4, 3.6 and 2.4 kb) for the LH/HCG receptor. LH/HCG receptor mRNA concentrations increased from preovulatory follicles to the corpus luteum of the midluteal phase, and decreased at the late luteal phase. Using in-situ hybridization, LH/HCG receptor mRNA was located predominantly in granulosa cells in the same follicle. Cloning of the human LH/HCG receptor cDNA previously revealed the existence of two alternative forms of the receptor differing by the presence (HLH-Ra) and absence (HLH-Rb) of 62 amino acids by exon 9. We have studied the functional significance of these receptor isoforms and have confirmed that they are generated by alternative splicing. A reverse transcription-polymerase chain reaction amplification was used to detect different isoforms of LH receptor mRNAs in ovary and placenta. The expression of the two mRNA forms of LH/HCG receptor were detected in ovary, and at very low concentrations in placenta. Treatment with HCG caused a dose-dependent increase in cAMP production with an initial response evident at approximately 1 ng/ml HCG in COS-7 cells expressing HLH-Ra. However, a complete loss of signal transduction was found in cells transfected with the truncated HLH-Rb.

PMID 9239715  Mol Hum Reprod. 1997 Feb;3(2):101-7.
著者: Norihiro Sugino
雑誌名: Reprod Med Biol. 2005 Mar;4(1):31-44. doi: 10.1007/BF03016135. Epub 2005 Mar 7.
Abstract/Text Cells living under aerobic conditions always face oxygen paradox. Oxygen is necessary for cells to maintain their lives. However, reactive oxygen species such as superoxide radical ( ), hydroxyl radical (OH-) and hydrogen peroxide (H2O2) are generated from oxygen and damage cells. Oxidative stress occurs as a consequence of excessive production of reactive oxygen species and impaired antioxidant defense systems. Antioxidant enzymes include: superoxide dismutase (SOD), which is a specific enzyme to scavenge superoxide radicals; copper-zinc SOD, located in the cytosol; and manganese SOD, located in the mitochondria. Both types of SOD belong to the first enzymatic step to scavenge superoxide radicals. It has been reported that a number of local factors such as cytokines, growth factors and eicosanoids are involved in the regulation of ovarian function, in addition to gonadotropins and ovarian steroid hormones. Since reactive oxygen species are generated and SOD is expressed in the ovary, there is a possibility that reactive oxygen species and SOD work as local regulators of ovarian function. The present review reports that reactive oxygen species and their scavenging systems play important roles in several processes of reproductive physiology, including follicular development, oocyte maturation, ovulation, corpus luteum function and follicular atresia. (Reprod Med Biol 2005; 4: 31- 45).

PMID 29699208  Reprod Med Biol. 2005 Mar;4(1):31-44. doi: 10.1007/BF03・・・
著者: Hirofumi Henmi, Toshiaki Endo, Yoshimitsu Kitajima, Kengo Manase, Hiroshi Hata, Ryuich Kudo
雑誌名: Fertil Steril. 2003 Aug;80(2):459-61.
Abstract/Text
PMID 12909517  Fertil Steril. 2003 Aug;80(2):459-61.
著者: Toshiaki Taketani, Hiroshi Tamura, Akihisa Takasaki, Lifa Lee, Fumie Kizuka, Isao Tamura, Ken Taniguchi, Ryo Maekawa, Hiromi Asada, Katsunori Shimamura, Russel J Reiter, Norihiro Sugino
雑誌名: J Pineal Res. 2011 Sep;51(2):207-13. doi: 10.1111/j.1600-079X.2011.00878.x. Epub 2011 May 17.
Abstract/Text This study investigated whether melatonin protects luteinized granulosa cells from reactive oxygen species (ROS) as an antioxidant to enhance progesterone production in the follicle during ovulation. Follicular fluid was sampled at the time of oocyte retrieval in women undergoing in vitro fertilization and embryo transfer (IVF-ET). Melatonin concentrations in the follicular fluid were positively correlated with progesterone concentrations (r = 0.342, P < 0.05) and negatively correlated with the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker (r = -0.342, P < 0.05). The progesterone and 8-OHdG concentrations were negatively correlated (r = -0.246, P < 0.05). Luteinized granulosa cells were obtained at the time of oocyte retrieval in women undergoing IVF-ET. Cells were incubated with H(2)O(2) (30, 50, 100 μm) in the presence or absence of melatonin (1, 10, 100 μg/mL). Progesterone production by luteinized granulosa cells was significantly inhibited by H(2)O(2). Melatonin treatment overcame the inhibitory effect of H(2) O(2) . Twenty-five patients who had luteal phase defect (serum progesterone concentrations <10 ng/mL during the mid-luteal phase) were divided into two groups during the next treatment cycle: 14 women were given melatonin (3 mg/day at 22:00 hr) throughout the luteal phase and 11 women were given no medication as a control. Melatonin treatment improved serum progesterone concentrations (>10 ng/mL during the mid-luteal phase) in nine of 14 women (64.3%), whereas only two of 11 women (18.1%) showed normal serum progesterone levels in the control group. In conclusion, melatonin protects granulosa cells undergoing luteinization from ROS in the follicle and contributes to luteinization for progesterone production during ovulation.

© 2011 John Wiley & Sons A/S.
PMID 21585519  J Pineal Res. 2011 Sep;51(2):207-13. doi: 10.1111/j.160・・・
著者: Norihiro Sugino, Aki Matsuoka, Ken Taniguchi, Hiroshi Tamura
雑誌名: Reprod Med Biol. 2008 Jun;7(2):91-103. doi: 10.1111/j.1447-0578.2008.00205.x. Epub 2008 Apr 17.
Abstract/Text Angiogenesis is important for the formation and development of the corpus luteum and for maintenance of luteal function. Blood vessel regression is an important physiological phenomenon in the corpus luteum, which is associated with tissue involution during structural luteolysis. Angiogenesis actively occurs during the early luteal phase and is completed by the mid-luteal phase. Perivascular cells (pericytes) increase in number from the early luteal phase to the mid-luteal phase, suggesting that blood vessels are gradually stabilized until the mid-luteal phase. In the corpus luteum undergoing luteolysis, blood vessels and pericytes decrease in number, which is related to structural involution. In the corpus luteum of early pregnancy, the number of blood vessels with pericytes increases, suggesting that angiogenesis occurs again, accompanied by blood vessel stabilization. These changes in vasculature of the corpus luteum are regulated by the collaboration with vascular endothelial growth factor, which is involved in proliferation of vascular endothelial cells, and angiopoietins, which are involved in stabilization of blood vessels. This review focuses on angiogenesis, blood vessel stabilization and blood vessel regression during the divergent phases of luteal formation, luteal regression and luteal rescue by pregnancy. (Reprod Med Biol 2008; 7: 91-103).

PMID 29699289  Reprod Med Biol. 2008 Jun;7(2):91-103. doi: 10.1111/j.1・・・
著者: Hiroshi Tamura, Akihisa Takasaki, Ken Taniguchi, Aki Matsuoka, Katsunori Shimamura, Norihiro Sugino
雑誌名: Fertil Steril. 2008 Dec;90(6):2334-9. doi: 10.1016/j.fertnstert.2007.10.056. Epub 2008 Feb 4.
Abstract/Text OBJECTIVE: To examine changes in blood flow in the corpus luteum throughout the luteal phase and during early pregnancy.
DESIGN: Longitudinal and cross-sectional prospective studies.
SETTING: University hospital and city general hospital.
PATIENT(S): Sixty-one women with normal menstrual cycles and normal luteal function, 13 women with hCG-induced ovulatory cycle, 10 women with luteal phase defect, six women with luteinized unruptured follicle (LUF), and 17 pregnant women (4-10 weeks of gestation).
INTERVENTION(S): Blood-flow impedance in the corpus luteum was assessed by transvaginal color-pulsed Doppler ultrasound.
MAIN OUTCOME MEASURES: Resistance index (RI) in the corpus luteum.
RESULT(S): In the normal menstrual cycle, the RI of the preovulatory follicle was high and significantly decreased after ovulation. Luteal-RI further decreased during the early to midluteal phase but significantly increased during the late luteal phase. Those changes in luteal-RI were similar to those of the hCG-induced ovulatory cycle. Luteal-RI during the midluteal phase was significantly higher in the patients with luteal phase defect than in women with normal luteal function. Luteal-RI of the LUF patients remained high throughout the luteal phase. In pregnant women, luteal-RI remained at the midluteal phase level until 7 weeks of gestation and significantly increased thereafter.
CONCLUSION(S): The change in luteal-RI was associated with corpus luteum development and corpus luteum regression. Luteal-RI was closely associated with luteal function.

PMID 18249380  Fertil Steril. 2008 Dec;90(6):2334-9. doi: 10.1016/j.fe・・・
著者: Akihisa Takasaki, Hiroshi Tamura, Ken Taniguchi, Hiromi Asada, Toshiaki Taketani, Aki Matsuoka, Yoshiaki Yamagata, Katsunori Shimamura, Hitoshi Morioka, Norihiro Sugino
雑誌名: J Ovarian Res. 2009 Jan 14;2:1. doi: 10.1186/1757-2215-2-1. Epub 2009 Jan 14.
Abstract/Text BACKGROUND: Blood flow in the corpus luteum (CL) is associated with luteal function. The present study was undertaken to investigate whether luteal function can be improved by increasing CL blood flow in women with luteal phase defect (LFD).
METHODS: Blood flow impedance in the CL was measured by transvaginal color-pulsed-Doppler-ultrasonography and was expressed as a resistance index (RI). The patients with both LFD [serum progesterone (P) concentrations < 10 ng/ml during mid-luteal phase] and high CL-RI (>/= 0.51) were given vitamin-E (600 mg/day, n = 18), L-arginine (6 g/day, n = 14) as a potential nitric oxide donor, melatonin (3 mg/day, n = 13) as an antioxidant, or HCG (2,000 IU/day, n = 10) during the subsequent menstrual cycle.
RESULTS: In the control group (n = 11), who received no medication to increase CL blood flow, only one patient (9%) improved in CL-RI and 2 patients (18%) improved in serum P. Vitamin-E improved CL-RI in 15 patients (83%) and improved serum P in 12 patients (67%). L-arginine improved CL-RI in all the patients (100%) and improved serum P in 10 patients (71%). HCG improved CL-RI in all the patients (100%) and improved serum P in 9 patients (90%). Melatonin had no significant effect.
CONCLUSION: Vitamin-E or L-arginine treatment improved luteal function by decreasing CL blood flow impedance. CL blood flow is a critical factor for luteal function.

PMID 19144154  J Ovarian Res. 2009 Jan 14;2:1. doi: 10.1186/1757-2215-・・・
著者: B M Biller, A Luciano, P G Crosignani, M Molitch, D Olive, R Rebar, J Sanfilippo, J Webster, H Zacur
雑誌名: J Reprod Med. 1999 Dec;44(12 Suppl):1075-84.
Abstract/Text Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis. While it can occur in men, it occurs more commonly in women. The prevalence of hyperprolactinemia ranges from 0.4% in an unselected normal adult population to as high as 9-17% in women with reproductive disorders. There are many possible causes of hyperprolactinemia, falling into three general categories: physiologic, pharmacologic and pathologic. When specific treatable underlying causes have been eliminated and in cases of severe hyperprolactinemia, the most likely cause is a prolactin (PRL)-secreting pituitary adenoma. Microadenomas should be treated medically, with a dopamine agonist, if there is an indication for therapy (such as amenorrhea, infertility or bothersome galactorrhea). If there is no indication for therapy, microadenomas may be followed conservatively, as growth is uncommon. Macroadenomas may grow larger; medical therapy is recommended initially, with neurosurgical evaluation reserved for specific clinical situations, such as failure of medical therapy and evidence of mass effect despite medical therapy. In the United States, the dopamine agonists indicated for treatment of hyperprolactinemia are bromocriptine and cabergoline. Bromocriptine is usually given once or twice daily, while cabergoline has a long duration of action and is given once or twice weekly. Results of comparative studies indicate that cabergoline is clearly superior to bromocriptine in efficacy (PRL suppression, restoration of gonadal function) and tolerability.

PMID 10649814  J Reprod Med. 1999 Dec;44(12 Suppl):1075-84.
著者: Ichiro Miwa, Hiroshi Tamura, Akihisa Takasaki, Yoshiaki Yamagata, Katsunori Shimamura, Norihiro Sugino
雑誌名: Fertil Steril. 2009 Apr;91(4):998-1004. doi: 10.1016/j.fertnstert.2008.01.029. Epub 2008 Mar 6.
Abstract/Text OBJECTIVE: To characterize pathophysiologic features of a "thin" endometrium.
DESIGN: A prospective observational study.
SETTING: University Hospital and City General Hospital.
PATIENT(S): Patients with normal-thickness endometrium (Normal-Em group: endometrial thickness >or=8 mm; n = 57) and thin endometrium (Thin-Em group: endometrial thickness <8 mm; n = 17).
MAIN OUTCOME MEASURE(S): Blood flow impedance of the uterine radial artery (RA) was assessed as resistance index (RI) by transvaginal color-pulsed Doppler ultrasonography. The area of glandular epithelium, the number of blood vessels, and vascular endothelial growth factor (VEGF) expression were examined in the midluteal-phase endometrium.
RESULT(S): The RA-RI in the Thin-Em group was significantly higher than in the Normal-Em group throughout the menstrual cycle. Endometrial thickness was significantly correlated with RA-RI. Growth of glandular epithelium, the number of blood vessels, and VEGF expression were significantly lower in the Thin-Em group than in the Normal-Em group.
CONCLUSION(S): A "thin" endometrium was characterized by high blood flow impedance of RA, poor epithelial growth, decreased VEGF expression, and poor vascular development.

PMID 18328483  Fertil Steril. 2009 Apr;91(4):998-1004. doi: 10.1016/j.・・・
著者: Akihisa Takasaki, Hiroshi Tamura, Ichiro Miwa, Toshiaki Taketani, Katsunori Shimamura, Norihiro Sugino
雑誌名: Fertil Steril. 2010 Apr;93(6):1851-8. doi: 10.1016/j.fertnstert.2008.12.062. Epub 2009 Feb 6.
Abstract/Text OBJECTIVE: To examine whether thin endometria can be improved by increasing uterine radial artery (uRA) blood flow.
DESIGN: A prospective observational study.
SETTING: University hospital and city general hospital.
PATIENT(S): Sixty-one patients with a thin endometrium (endometrial thickness [EM] <8 mm) and high radial artery-resistance index of uRA (RA-RI >or=0.81).
INTERVENTION(S): Vitamin E (600 mg/day, n = 25), l-arginine (6 g/day, n = 9), or sildenafil citrate (100 mg/day, intravaginally, n = 12) was given.
MAIN OUTCOME MEASURE(S): EM and RA-RI were assessed by transvaginal color-pulsed Doppler ultrasound.
RESULT(S): Vitamin E improved RA-RI in 18 (72%) out of 25 patients and EM in 13 (52%) out of 25 patients. L-arginine improved RA-RI in eight (89%) out of nine patients and EM in six (67%) patients. Sildenafil citrate improved RA-RI and EM in 11 (92%) out of 12 patients. In the control group (n = 10), who received no medication to increase uRA-blood flow, only one (10%) patient improved in RA-RI and EM. The effect of vitamin E was histologically examined in the endometrium (n = 5). Vitamin E improved the glandular epithelial growth, development of blood vessels, and vascular endothelial growth factor protein expression in the endometrium.
CONCLUSION(S): Vitamin E, l-arginine, or sildenafil citrate treatment improves RA-RI and EM and may be useful for the patients with a thin endometrium.

Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
PMID 19200982  Fertil Steril. 2010 Apr;93(6):1851-8. doi: 10.1016/j.fe・・・

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